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Although there is a growing interest in the role of gastric microbiome on the development of gastric cancer, the exact mechanism is largely unknown. We aimed to investigate the changes of gastric microbiome during gastric carcinogenesis, and to predict the functional potentials of the microbiome involved in the cancer development. The gastric microbiome was analyzed using gastric juice samples from 88 prospectively enrolled patients, who were classified into gastritis, gastric adenoma, or early/advanced gastric cancer group. Differences in microbial diversity and composition were analyzed with 16S rRNA gene profiling, using next-generation sequencing method. Metagenomic biomarkers were selected using logistic regression models, based on relative abundances at genus level. We used Tax4Fun to predict possible functional pathways of gastric microbiome involved in the carcinogenesis. The microbial diversity continuously decreased in its sequential process of gastric carcinogenesis, from gastritis to gastric cancer. The microbial composition was significantly different among the four groups of each disease status, as well as between the cancer group and non-cancer group. Gastritis group was differently enriched with genera Akkermansia and Lachnospiraceae NK4A136 Group , whereas the cancer group was enriched with Lactobacillus and Veillonella . Predictive analysis of the functional capacity of the microbiome suggested enrichment or depletion of several functional pathways related to carcinogenesis in the cancer group. There are significant changes in the diversity and composition of gastric microbiome during the gastric carcinogenesis process. Gastric cancer was characterized with microbial dysbiosis, along with functional changes potentially favoring carcinogenesis.

Colorectal cancer (CRC) is the most common type cancers in the world. CRC occurs sporadically in the majority of cases, indicating the predominant cause of the disease are environmental factors. Diet-induced changes in gut-microbiome are recently supposed to contribute on epidemics of CRC. This study was aimed to investigate the association of metagenomics and metabolomics in gut extracellular vesicles (EVs) of CRC and healthy subjects. A total of 40 healthy volunteers and 32 patients with CRC were enrolled in this study. Metagenomic profiling by sequencing 16 S rDNA was performed for assessing microbial codiversity. We explored the small molecule metabolites using gas chromatography-time-of-flight mass spectrometry. In total, stool EVs were prepared from 40 healthy volunteers and 32 patients with CRC. Metagenomic profiling demonstrated that bacterial phyla, particularly of Firmicutes and Proteobacteria , were significantly altered in patients with colorectal cancer. Through metabolomics profiling, we determined seven amino acids, four carboxylic acids, and four fatty acids; including short-chain to long chain fatty acids that altered in the disease group. Binary logistic regression was further tested to evaluate the diagnostic performance. In summary, the present findings suggest that gut flora dysbiosis may result in alternation of amino acid metabolism, which may be correlated with the pathogenesis of CRC.

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic immune-mediated intestinal inflammatory disorders associated with microbial dysbiosis at multiple sites, particularly the gut. Anti-tumor necrosis factor-α (TNF-α) agents are important treatments for IBD. We investigated whether microbiome changes at multiple sites can predict the effectiveness of such treatment in IBD. Stool, saliva, serum, and urine biosamples were collected from 19 IBD patients before (V1) and 3 months after (V2) anti-TNF-α treatment, and 19 healthy subjects (control). Microbiota analysis was performed using extracellular vesicles (EVs; all four sample types) and next-generation sequencing (NGS; stool and saliva). The stool, using NGS analysis, was the only sample type in which α-diversity differed significantly between the IBD and control groups at V1 and V2. Relative to non-responders, responders to anti-TNF-α treatment had significantly higher levels of Firmicutes (phylum), Clostridia (class), and Ruminococcaceae (family) in V1 stool, and Prevotella in V1 saliva. Non-responders had significantly higher V2 serum and urine levels of Lachnospiraceae than responders. Finally, Acidovorax caeni was detected in all V1 sample types in responders, but was not detected in non-responders. Microbiome changes at multiple sites may predict the effectiveness of anti-TNF-α treatment in IBD, warranting further research.

Colorectal cancer (CRC) is the third most common form of cancer and poses a critical public health threat due to the global spread of westernized diets high in meat, cholesterol, and fat. Although the link between diet and colorectal cancer has been well established, the mediating role of the gut microbiota remains elusive. In this study, we sought to elucidate the connection between the gut microbiota, diet, and CRC through metagenomic analysis of bacteria isolated from the stool of CRC ( n  = 89) and healthy ( n  = 161) subjects. This analysis yielded a dozen genera that were significantly altered in CRC patients, including increased Bacteroides , Fusobacterium , Dorea , and Porphyromonas prevalence and diminished Pseudomonas , Prevotella , Acinetobacter , and Catenibacterium carriage. Based on these altered genera, we developed two novel CRC diagnostic models through stepwise selection and a simplified model using two increased and two decreased genera. As both models yielded strong AUC values above 0.8, the simplified model was applied to assess diet-based CRC risk in mice. Mice fed a westernized high-fat diet (HFD) showed greater CRC risk than mice fed a regular chow diet. Furthermore, we found that nonglutinous rice, glutinous rice, and sorghum consumption reduced CRC risk in HFD-fed mice. Collectively, these findings support the critical mediating role of the gut microbiota in diet-induced CRC risk as well as the potential of dietary grain intake to reduce microbiota-associated CRC risk. Further study is required to validate the diagnostic prediction models developed in this study as well as the preventive potential of grain consumption to reduce CRC risk. Colorectal cancer: Factors influencing cancer risk Tracing biomarkers of gut bacteria sheds light on how diet can affect gut composition and the risk of developing colorectal cancer (CRC). CRC is linked to diet, and scientists are examining how diet-associated changes in the gut microbiome may influence cancer risk. Yoon-Keun Kim, MD Healthcare Inc., Seoul, and Young-Koo Jee, Dankook University College of Medicine, Cheonan, South Korea, and co-workers analyzed bacterial populations in fecal samples from 89 CRC patients and 161 healthy controls. They found significant differences between patients and controls in 16 bacterial genera, these differences being potential biomarkers in diagnostic models for assessing CRC risk. The researchers used the models to determine CRC risk in mice fed diets, and found that the predicted risk was considerably reduced in mice on grain diets, especially rice or sorghum, compared to high fat diets.

Synbiotics, the combination of probiotics and prebiotics, are known to confer health benefits via intestinal microbiota modulation. However, significant intestinal microbiota alterations can be difficult to determine in intervention studies based on solely bacterial stool metagenomic analysis. Intestinal microbiota constituents secrete 20–200-nm-sized extracellular vesicles (EVs) containing microbial DNA, proteins, and lipids that are distributed throughout the body, providing an alternative target for microbiota metagenomic analysis. Here, we determined the impact of a synbiotic beverage enriched with the kimchi-derived bacterium Leuconostoc holzapfelii ( L . holzapfelii ) on the intestinal microbiota and local and circulatory microbiota-derived EV composition of healthy Korean adults. We isolated microbial DNA from stool bacteria, stool EVs, and urinary EVs and conducted next-generation sequencing of the 16S rDNA V3–V4 regions before and after synbiotic consumption. The species diversity of circulating urinary EVs was significantly increased after synbiotic consumption, while stool bacterial and EV diversity remained unchanged. Furthermore, we found that while a single genus was decreased among the stool bacteria constituents, stool EVs and urinary EVs showed significant alterations in four and eight genera, respectively. Blood chemistry assays revealed that synbiotic consumption significantly lowered aspartate aminotransferase (AST) serum levels, particularly in subjects with starting levels above the normal range (>40 UI/L). In conclusion, the L . holzapfelii- enriched synbiotic beverage greatly altered serum AST levels and microbial EV composition in urine and stool, while only minor changes were observed in the gut microbiota composition. Based on these findings, we suggest the potential use of microbiota-derived EVs as surrogate markers in future predictive diagnosis studies. Gut microbes: Vesicles reveal variations in populations Analyzing the contents of small membrane-bound sacs called extracellular vesicles (EVs) that are released by microbes in the gut, and which can readily be sampled in stools and urine, offers an effective way to monitor gut microbial populations. Bacteria known as probiotics and chemicals that sustain them called prebiotics are commonly used to encourage health-promoting changes in gut microbe content. Detecting any changes by analyzing the bacteria in stools, however, has proved difficult. Researchers in South Korea led by Yoon-Keun Kim of MD Healthcare Inc., Seoul, and Young-Koo Jee at Dankook University, Cheonan, found that analyzing microbial EVs in stools or urine detected changes more effectively. They analyzed EVs after administering a synbiotic drink – a mixture of probiotics and prebiotics. EV analysis could assist diagnosis of health problems associated with changes in gut microbial populations.

Dysbiosis is an environmental factor that affects the induction of axial spondyloarthritis (axSpA) pathogenesis. In the present study, we investigated differences in the gut microbiota of patients with axSpA and revealed an association between specific gut microbiota and their metabolites, and SpA pathogenesis. Using 16S rRNA sequencing data derived from feces samples of 33 axSpA patients and 20 healthy controls (HCs), we examined the compositions of their gut microbiomes. As a result, axSpA patients were found to have decreased α-diversity compared to HCs, indicating that axSpA patients have less diverse microbiomes. In particular, at the species level, and were more abundant in axSpA patients than in HCs, whereas , a butyrate-producing bacteria, was more abundant in HCs. Thus, we decided to investigate whether was associated with health conditions by inoculating (0.1, 1, and 10 μg/mL) or by administrating butyrate (0.5 mM) into CD4 T cells derived from axSpA patients. The levels of IL-17A and IL-10 in the CD4 T cell culture media were then measured. We also assessed osteoclast formation by administrating butyrate to the axSpA-derived peripheral blood mononuclear cells. The CD4 IL-17A T cell differentiation, IL-17A levels were decreased, whereas IL-10 was increased by inoculation. Butyrate reduced CD4 IL-17A T cell differentiation and osteoclastogenesis. We found that CD4 IL-17A T cell polarization was reduced, when or butyrate were introduced into curdlan-induced SpA mice or CD4 T cells of axSpA patient. Consistently, butyrate treatment was associated with the reduction of arthritis scores and inflammation levels in SpA mice. Taken together, we concluded that the reduced abundance of butyrate-producing microbes, particularly , may be associated with axSpA pathogenesis.

Background/Objectives: Gastric cancer treatments can lead to significant alterations to patients’ gastrointestinal microbiome. However, differences in microbial impacts between gastrectomy and endoscopic submucosal dissection (ESD) remain underexplored. This study investigates how these treatments influence microbial diversity and composition in patients with stage I gastric cancer. Methods: Patients with pathologically confirmed stage I gastric cancer were recruited from Chung-Ang University Hospital between December 2016 and December 2019. This study analyzed fecal samples from 13 patients (ESD: n = 5; gastrectomy: n = 8) before and after treatment using 16S rRNA gene sequencing. Microbial diversity indices and taxonomic composition were compared, with follow-up extending up to two years. Results: In the total cohort, alpha diversity significantly decreased post-treatment (p < 0.05), and beta diversity analysis showed distinct clustering between pre- and post-treatment samples (p < 0.05). At the genus level, Bacteroides significantly decreased (p < 0.05), while Lactobacillus, Bifidobacterium, and Blautia showed significant increases (p < 0.05). Comparative analyses revealed that in the ESD group, alpha diversity remained unchanged, although beta diversity showed significant clustering (p < 0.05), without notable changes in major taxa. In contrast, surgical resection resulted in a significant reduction in alpha diversity (p < 0.05) and beta diversity clustering (p < 0.05), with increased abundances of Streptococcus and Blautia and decreased abundance of Bacteroides (p < 0.05). Conclusions: Surgical gastrectomy exerts significant effects on microbiome diversity and composition, while ESD has a more limited impact. These findings underscore the importance of considering microbiome changes in postoperative management.

Obesity associated with a Western diet such as a high-fat diet (HFD) is a known risk factor for inflammatory bowel disease (IBD) and colorectal cancer (CRC). In this study, we aimed to develop fecal microbiome data-based deep learning algorithms for the risk assessment of colorectal diseases. The effects of a HFD and a candidate food (Nypa fruticans, NF) on IBD and CRC risk reduction were also evaluated. Fecal microbiome data were obtained from 109 IBD patients, 111 CRC patients, and 395 healthy control (HC) subjects by 16S rDNA amplicon sequencing. IBD and CRC risk assessment prediction models were then constructed by deep learning algorithms. Dietary effects were evaluated based on fecal microbiome data from rats fed on a regular chow diet (RCD), HFD, and HFD plus ethanol extracts or water extracts of NF. There were significant differences in taxa when IBD and CRC were compared with HC. The diagnostic performance (area under curve, AUC) of the deep learning algorithm was 0.84 for IBD and 0.80 for CRC prediction. Based on the rat fecal microbiome data, IBD and CRC risks were increased in HFD-fed rats versus RCD-fed rats. Interestingly, in the HFD-induced obesity model, the IBD and CRC risk scores were significantly lowered by the administration of ethanol extracts of NF, but not by the administration of water extracts of NF. In conclusion, changes in the fecal microbiome of obesity by Western diet could be important risk factors for the development of IBD and CRC. The risk prediction model developed in this study could be used to evaluate dietary efficacy.

Human microbiota refers to living microorganisms which colonize our body and crucially contribute to the metabolism of nutrients and various physiologic functions. According to recently accumulated evidence, human microbiota dysbiosis in the genital tract or pelvic cavity could be involved in the pathogenesis and/or pathophysiology of endometriosis. We aimed to investigate whether the composition of microbiome is altered in the peritoneal fluid in women with endometriosis. We recruited 45 women with histological evidence of ovarian endometrioma and 45 surgical controls without endometriosis. Following the isolation of extracellular vesicles from peritoneal fluid samples from women with and without endometriosis, bacterial genomic DNA was sequenced using next-generation sequencing of the 16S rDNA V3–V4 regions. Diversity analysis showed significant differences in the microbial community at phylum, class, order, family, and genus levels between the two groups. The abundance of Acinetobacter, Pseudomonas, Streptococcus, and Enhydrobacter significantly increased while the abundance of Propionibacterium, Actinomyces, and Rothia significantly decreased in the endometriosis group compared with those in the control group (p < 0.05). These findings strongly suggest that microbiome composition is altered in the peritoneal environment in women with endometriosis. Further studies are necessary to verify whether dysbiosis itself can cause establishment and/or progression of endometriosis.

Synbiotics, the combination of probiotics and prebiotics, are known to confer health benefits via intestinal microbiota modulation. However, significant intestinal microbiota alterations can be difficult to determine in intervention studies based on solely bacterial stool metagenomic analysis. Intestinal microbiota constituents secrete 20–200-nm-sized extracellular vesicles (EVs) containing microbial DNA, proteins, and lipids that are distributed throughout the body, providing an alternative target for microbiota metagenomic analysis. Here, we determined the impact of a synbiotic beverage enriched with the kimchi-derived bacterium Leuconostoc holzapfelii (L. holzapfelii) on the intestinal microbiota and local and circulatory microbiota-derived EV composition of healthy Korean adults. We isolated microbial DNA from stool bacteria, stool EVs, and urinary EVs and conducted next-generation sequencing of the 16S rDNA V3–V4 regions before and after synbiotic consumption. The species diversity of circulating urinary EVs was significantly increased after synbiotic consumption, while stool bacterial and EV diversity remained unchanged. Furthermore, we found that while a single genus was decreased among the stool bacteria constituents, stool EVs and urinary EVs showed significant alterations in four and eight genera, respectively. Blood chemistry assays revealed that synbiotic consumption significantly lowered aspartate aminotransferase (AST) serum levels, particularly in subjects with starting levels above the normal range (>40 UI/L). In conclusion, the L. holzapfelii-enriched synbiotic beverage greatly altered serum AST levels and microbial EV composition in urine and stool, while only minor changes were observed in the gut microbiota composition. Based on these findings, we suggest the potential use of microbiota-derived EVs as surrogate markers in future predictive diagnosis studies. KCI Citation Count: 28